This invention relates in general to methods and means for therapeutic medical treatment. More particularly, the invention involves an interstitial or intracavitary probe containing an antenna or radiator adapted to deliver microwave energy and ionizing radiation to living tissue within a human or animal body. The invention includes a novel method for simultaneously or sequentially delivering these forms of energy within ranges which are capable of destroying tumorous tissue while avoiding damage to viable tissue. This invention provides an efficient and effective means for implementing the synergistic necrotic effects of the simultaneous or sequential application of hyperthermia and ionizing radiation to tumors, and in particular deeply internal tumors, and particularly tumors of the brain, breast, esophagus, colon-rectum, cervix, vagina, bile duct, bronchus, and other sites now considered for interstitial or intracavitary radiation therapy.
In cancer therapy, failure to control local disease is a major cause of mortality and morbidity. Persistent local disease following conventional therapy occurs in about 30% of all the cases. Attempts at improving local control by radiosensitizers or combinations of chemo/radiotherapy have not had a significant impact. In cases where high doses of radiation can be delivered, the local control or cure rates have been excellent. In most cases, the dose limiting factor is the tolerance of the surrounding tissue. In order to overcome this difficulty, interstitial or intracavitary irradiation has been used for decades as an adjunct to external irradiation. At present, there is a resurgence in the use of intracavitary and interstitial irradiation due to several factors. These include the utilization of new radionuclides, the realization that the expected results of radiosensitizers or chemotherapy have not materialized, and the development of expertise by radiologists in the techniques of interventional radiology.
The results of previous studies using radiation and hyperthermia suggest that the response rates are double the response rate from radiation alone. It seems that the combination of hyperthermia and interstitial irradiation would be of benefit. Regions which would benefit the most from a hyperthermia-interstitial radiotherapy approach would include those cases where there is a high probability of local failure following external irradiation. Examples include brain tumors, sarcomas, melanomas, renal cell carcinoma, advanced head and neck and cervical cancer. Hyperthermia interstitial radiotherapy is also beneficial in treating cases where the surrounding tolerance of normal tissue limits the doses of external irradiation and hence curative external doses cannot be delivered. Examples would include carcinoma of the pancreas, esophagus, gall bladder and common bile duct.
The principle advantage of a technique combining interstitial radiation and hyperthermia would be the administration of irradiation and heat to a limited tumor volume while sparing the surrounding normal tissues.
At present, interstitial stereotactic radiotherapy in brain tumors is in progress. The development of an interstitial dual modality probe would provide an opportunity to enhance the radiation effectiveness in gliomas which are notorious for their radioresistance.
Cancer of the esophagus is rarely cured by irradiation although palliation is easily achieved. In Britain, several centers have adopted a new afterloading applicator to improve their results by intracavitary irradiation. Their aim is:
1. To convert inoperable patients to operable patients PA1 2. Irradiate the entire esophagus with a localized high dose PA1 3. Boost external beam therapy PA1 4. Obtain cheap, quick palliation in incurable cases
Combining these techniques with hyperthermia should result in significant clinical improvement.
lntracavitary techniques can also be used to improve the results in carcinoma of the common bile duct. Several recent reports have shown that combined external and interstitial irradiation is producing better results than surgery or irradiation alone. When combined with hyperthermia, intracavitary results should be even more impressive.
Limited lung cancer that is non-resectable due to adherence to surrounding structures are benefitted by interstitial radiotherapy. Again, combination with hyperthermia should yield better results.
Pancreatic cancers at present are treated mainly for palliation because of poor tolerance of surrounding tissue to external irradiation. Interstitial radiotherapy with hyperthermia should prove beneficial since most of those patients, many of whom die from local failure, undergo surgery and could have interstitial radiotherapy combined with local hyperthermia.
Often, potentially resectable tumors cannot be totally resected because the disease is adjacent to sensitive organs such as blood vessels or nerves. In these cases, external irradiation is often limited to the tolerance of surrounding tissue. The use of both hyperthermia and interstitial radiotherapy will allow curative doses of radiotherapy and a reduced dose to normal tissues due to the interstitial approach to radiation therapy.
Other areas where local control of disease is less than optimal includes recurrent head and breast cancer. In all of these cases, interstitial radiotherapy and hyperthermia should result in improved local control and better osmesis.
In short, the dual modality probe could initially be used in cases of recurrent tumors or accessible superficial lesions where implantation is indicated. It has wide implication for palliation, adjuvant and curative treatment.
The use of interstitial techniques in hyperthermia was suggested in 1975. Because of the complexity of the treatments and the collaboration required between disciplines of clinical hyperthermia and brachytherapy, very few centers have been dealing with these interstitial procedures.
The hyperthermia group at Tucson (University of Arizona) was one of the first to develop clinical interstitial forms of thermo-radiotherapy. They used resistive diathermy by means of radiofrequency electric currents (in a range 0.5-1 MHz) driven between pairs of arrays of implanted metallic needles. These needles were then loaded with Ir.sup.192 wires, the complimentary radiation dose being approximately half the value of the usual "curative" brachytherapy dose.
Considering the encouraging preliminary results obtained in Tucson, several groups began to use interstitial resistive diathermy either in the same way or with modified techniques.
At the same time, other centers were developing means of producing interstitial thermotherapy using radiative heating by means of microwave antenna inserted into implanted plastic catheters using a frequency range from 300-1000 MHz. In general, this technique was followed by brachytherapy.
Other groups, particularly in the United States, are studying the use of implanted ferromagnetic seeds which can be inductively heated by high frequency, alternating magnetic fields. Newly designed, self-regulating thermoseeds using a Curie point switch have shown some promise.
In the data obtained in these centers, it appeared that interstitial techniques were able to achieve the required increase in tumor temperature in a large number of cases. In addition, the distribution of temperature was usually satisfactory with acceptable temperature profiles in the heated volume. The development of a technique as proposed in this document will ultimately make this thermo-radiation therapy approach more appealing to many physicians because of reduced complexity, ease of use and commercial availability of proven technology.
Hyperthermia has been studied extensively to determine its efficacy in the treatment of human neoplasm. In vitro work has demonstrated that hyperthermia can kill mammalian cells in a temperature and time dependent manner. The degree of cell kill has been shown to depend upon many factors. The microenvironment of the tumor is often conducive to hyperthermia cell killing because of such factors as low pH, anoxia, nutrient deficiency and altered cell cycle distribution. Hyperthermia as a sole modality is felt to have little potential value, but in combination with radiotherapy, preliminary studies are very positive.
The exact mechanism for thermal radio sensitization is not known. However, the mechanism is known to be synergistic and has a time-temperature dependence. The complimentary nature of these two modalities must not be understated. Typically, the conditions for radioresistance such as hypoxia, low pH, and cells in S phase are the conditions under which hyperthermia is most effective.
A significant amount of data has been complied to describe (if not explain) the synergistic nature of thermal radiotherapy. The reduction of the radiation survival curve would indicate an inhibition in the cells ability to accumulate and repair sublethal damage (SLD).
The rationale for the use of hyperthermia in conjunction with radiotherapy is well established. The role of hyperthermia in combination with interstitial low dose rate (LODR) radiotherapy may be even more important. It is well known that the combined application of heat and radiotherapy is more effective than exclusive use of either therapy. Simultaneous or overlapping treatment of heat and radiotherapy is inherent with the type of probe proposed. A second very important reason for designing a probe of the nature being proposed is the correlation between thermal sensitization and radiation damage as a function of radiation dose rate. Several studies have shown that the degree of thermal enhancement of radiation sensitivity is greater at low dose rates. For intracavitary and interstitial radiotherapy, the dose rate at the tumor periphery will be of the order of 40 rads/hour, which is typical of LDR radiotherapy.
Thus, while the therapeutic value of the combined application of ionizing radiation and hyperthermia are recognized, the systems for providing this synergistic benefit have been primarily of an experimental nature and characterized by complex, expensive, and cumbersome equipment inappropriate for use in day to day clinical environment.
These and other difficulties experienced with prior art devices have been obviated in a novel manner by the present invention.
It is, therefore, an outstanding object of this invention to provide a compact antenna or radiator capable of simultaneously or sequentially delivering microwave energy and ionizing radiation to tissue within a living organism.
It is another object of the invention to provide a probe bearing a microwave antenna which is adapted for insertion of an ionizing radiation source.
It is a further object of the invention to provide a device for warming target tissue with a probe carrying a microwave antenna and then subsequently introducing an ionizing radiation source via the same probe.
Another object of this invention is to provide a device which allows withdrawal of the ionizing radiation source while microwave heating continues.
Another object of this invention is the provision of a microwave and ionizing radiator which is simple in construction and use and capable of a long and useful life with a minimum of maintenance and expense.
With these and other objects in view, as will be apparent to those skilled in the art, the invention resides in the combination of parts set forth in the specification and covered by the claims appended hereto.